Sequential treatment of metformin and clomiphene citrate in clomiphene-resistant women with polycystic ovary syndrome: a randomized, controlled trial

Hum Reprod. 2003 Feb;18(2):299-304. doi: 10.1093/humrep/deg105.

Abstract

Background: Recognition of the importance of insulin resistance in clomiphene-resistant women with polycystic ovary syndrome (PCOS) has led to the use of insulin sensitizers.

Methods: A randomized, controlled trial was conducted to compare efficacy of sequential treatment with metformin and clomiphene citrate with conventional gonadotrophins. Sixty clomiphene-resistant women with PCOS were randomized to two groups (n = 30 each), using computer-generated tables. Group I received metformin for 6 months, followed by ovulation induction with clomiphene citrate; group II received hMG for ovulation induction. Hormonal profiles were evaluated at the onset and after completion of treatment.

Results: There was no significant difference in pregnancy rates between the two groups (16.7 versus 23.3%). In group I, there was a significant improvement in menstrual function and ovulation after treatment (40%, P < 0.001; and 46.7%, P < 0.001), with a significant decrease in fasting insulin levels (P < 0.05). There were no changes in other biochemical parameters. The ovulation rate in group II was 43.3%, with a high drop-out rate. The cost-effective analysis for medications per pregnancy in group I was US$ 71 +/- 3 versus US$ 277 +/- 171 in group II.

Conclusions: Sequential treatment with metformin and clomiphene citrate is an effective and safe option for clomiphene-resistant women with PCOS.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Clomiphene / therapeutic use*
  • Cost-Benefit Analysis
  • Drug Resistance
  • Drug Therapy, Combination
  • Fasting / blood
  • Female
  • Fertility Agents, Female / therapeutic use*
  • Health Care Costs
  • Humans
  • Insulin / blood
  • Menotropins / therapeutic use
  • Menstruation / drug effects
  • Metformin / therapeutic use*
  • Ovulation / drug effects
  • Ovulation Induction*
  • Polycystic Ovary Syndrome / drug therapy*
  • Pregnancy
  • Pregnancy Rate

Substances

  • Fertility Agents, Female
  • Insulin
  • Clomiphene
  • Menotropins
  • Metformin